This invention belongs to the fields of animal husbandry and pharmaceutical chemistry, and provides a superior sustained release injectable formulation of bovine somatotropin, a polypeptide growth hormone which has long been the subject of research. Its structure and properties are discussed by Wallis and Davies, in Pecile and Muller, Editors, Growth Hormone and Related Peptides, Excerpta Medica, Amsterdam, 1967, pp. 1-13.
The earlier work with animal hormones, such as bovine somatotropin, was characterized by difficulty in obtaining amounts of the hormones sufficient for useful experiments. The hormones could be obtained only by isolation from the appropriate glandular tissue of animals, and the procedures were tedious and wasteful in the extreme. See, for example, an article by Reichert on the purification of anterior pituitary hormones, including bovine growth hormone, at page 360-380 of Methods in Enzymology, Vol. 37.
More recently, experimentation in animals with bovine somatotropin has become feasible on a large scale because of the development, by genetic modification methods, of microorganisms which can produce the hormones in vitro.
A number of processes for preparing bovine somatotropin by use of such microorganisms have been published. It should be noted that some of the modified microorganisms produce a modified somatotropin, typically modified by bearing one or a few extra amino acids on an end of the polypeptide chain. According to the literature, these modified hormones have the same properties and activity as does natural bovine somatotropin. Accordingly, throughout this document, the term "bovine somatotropin" is used to include modified bovine somatotropins, synthesized by genetically modified microorganisms, which share the properties and activity of natural bovine somatotropin.
The following group of patent documents and publications describe modified microorganisms, and processes making use of such microorganisms, which synthesize bovine somatotropin.
Mayne, et al., European Patent Publication No. 0095361
George, et al., European Patent Publication No. 0111814
Rottman, et al., European Patent Publication No. 0067026
Miller, et al., European Patent Publication No. 0047600
Frazer, et al., European Patent Publication No. 0068646
Aviv, et al., British Patent Application No. 2073245
De Boer, et al., European Patent Publication No. 0075444
Schoner, et al., Biotechnology, Feb. 1985, 151-154
Schoner, et al., Proc. Nat. Acad. Sci. USA 81, 5403-07 (1984)
It has been known for more than 35 years that bovine somatotropin, administered to dairy cows, will increase the yield of milk without adversely affecting the composition of it. Cotes, et al., Nature 164, 992 (1949). Numerous experiments were carried out, following the work of Cotes and his group, to explore further the relationship between somatotropin and increased milk yield in dairy cattle, and more recently the focus has shifted to experiments with somatotropin produced by genetically modified microorganisms. For example, see Eppard, et al., Proc. Cornell Nutr. Conf., 1984, p. 5. Some workers report that microorganism-synthesized bovine somatotropin is even more effective in increasing milk yield than is the natural hormone. DeGoeter, et al., European Patent Publication No. 0085036.